Breast Cancer and New Treatments Breast Cancer affects one in eight of American women, and is the second most common cause of cancer death in America. I chose to write my term paper on breast cancer because it is a disease that has effected some members of my family. Due to this possibly inherited condition, I felt that researching the topic would help me learn ways to prevent the disease and educate myself to perform self-exams that may result in early detection. Breast cancer is a malignant tumor in the glandular tissues of the breast. Such tumors, also called carcinomas, form when the chemical processes that control normal cell growth break down, enabling a single abnormal cell to multiply at a rapid rate (Hickman). Carcinomas, which tend to destroy an increasing proportion of normal breast tissue over time, may spread, or metastasize, to other parts of the body.

Breast cancer is the most common cancer in women, other than skin cancer. A major health problem in many parts of the world, it is especially prevalent in developed countries. The American Cancer Society (ACS) estimates that in the United States more than 175, 000 new cases are diagnosed and more than 43, 000 women die each year from cancer originating in the breast. One in eight American women will develop this illness at some time during her life (Cummings). The rate of incidence increases with age, and women 75 years and older are at the highest risk.

Breast cancer can affect males, but the disease strikes women about 100 times as often as it does men. The good news is that if a woman develops breast cancer, her options are much greater than ever before due to advancements in technology, and proper treatment can usually preserve the breast while enhancing survival (Feldman). Scientists do not understand exactly what causes breast cancer. Studies suggest that several categories of women are at increased risk for the disease those who began to menstruate at an unusually early age; those who experienced menopause, or the permanent cessation of menstruation, at an unusually late age; those who waited until later in life to have children; and those who never gave birth.

Such findings, all of which relate to hormone-based life events, suggest that breast cancer is somehow affected by prolonged exposure to female sex hormones, such as estrogen. Women with a history of breast cancer in the family are also at greater risk. About five percent of all breast cancers have been attributed to a mutated, or structurally altered, gene known as BRCA 1. Mutations in a second gene, BRCA 2, contribute significantly to the development of breast cancer in Jewish women.

Alcohol, high levels of fat in the diet, and not exercising regularly have also been linked to increased risk for breast cancer (Garber). Three-quarters of all breast cancer patients are not in any of the groups considered at increased risk for breast cancer, indicating that not all risk factors are understood. As a result, doctors recommend that every woman should familiarize herself with the techniques for monthly breast self-examination. X-ray examination of the breasts, a technique called mammography, can detect tumors before they are large enough to be felt and increase the odds for successful treatment. The American Cancer Society recommends that women over age 40 should have a mammogram every year.

The only way to make a positive diagnosis on a suspect lump in the breast is by having a biopsy, a minor surgical procedure in which the lump or part of the lump is removed and examined under a microscope. The most common sites of metastasis in breast cancer patients are the lymph glands located in the armpit. The presence or absence of cancer cells in the lymph glands helps physicians determine how far the cancer has advanced and whether a woman is likely to be cured by mastectomy, the surgical removal of the breast (Garber). Removal of a cancerous tumor by surgery cures one-third of all breast cancers that are detected early. If only the lump and some surrounding breast tissue are removed, leaving most of the breast intact, the procedure is called a partial mastectomy, or lumpectomy.

When the breast and other tissues surrounding it are removed, the operation is termed a radical mastectomy. In some cases, radiation therapy is recommended in addition to surgery to treat cancer that has not spread beyond the breast. Traditionally, breast cancer treatment relies heavily on radiation, surgical removal of the breast, called mastectomy, and cytotoxic chemotherapy. There are four stages of breast cancer. The first stage is a tumor less than two centimeters in diameter, where nodes are not involved and there is no distant metastasis. The second stage is a tumor that is less than five centimeters and has no distant metastasis.

The third stage is a tumor that is greater than five centimeters in diameter, is invading the skin, and has no distant metastasis. The fourth and final stage of breast cancer includes a tumor that has distant metastasis. The survival rates for each of these stages include 85% for stage one, 66% for stage two, 41% for stage three, and 10% for stage four (Feldman). At the present, clinical research in breast cancer is focusing on a variety of promising therapeutic strategies, such as new chemotherapy agents, endocrine agents, antibody therapy, vaccines, and anti angiogenesis agents.

A number of drugs are under investigation for treating breast cancer, some of which have shown considerable promise in reducing the size of tumors, and even preventing the disease. They include drugs called taxol, tamoxifen, and Herceptin, which each work to improve the effectiveness of chemotherapy (Gradishar). The drug taxol, approved in 1992 by the FDA for treating breast, ovarian and other types of cancers, is extracted from the bark of the Pacific yew. The tree is scarce, however, and large amounts of taxol are needed for treatment. Scientists are studying the feasibility of cultivating the trees to harvest the drug from the bark, as well as the possibility of extracting the drug from the branches and needles. Taxol, also called paclitaxel, is an antineoplastic and is usually administered by injection and used to treat advanced breast cancer.

Chemotherapy, and the administration of cancer-fighting drugs, such as taxol, has proven effective in destroying breast cancer cells that have spread to other organs. This drug works on the microtubules of the cell preventing with interphase and mitotic cell functions, which is one of the steps in cell division and multiplication. Side effects include hypersensitivity reactions, bone marrow suppression, blood pressure excursions and muscle pain, damage to the nerves of the hands and feet, nausea, vomiting, and hair loss. Preliminary results of clinical trials have showed that taxol, when given with standard chemotherapy, improved patient survival rates by 26%, and reduced the risk of reoccurrence by 22%. Another alternative is docetaxel, a substance that is similar to paclitaxel. Docetaxel comes from the needles of the yew tree.

This drug is FDA approved to treat advanced breast cancer that has not responded to other anticancer drugs. The side effects of docetaxel are similar to those related to paclitaxel ("Paclitaxel (Taxol) and Other Related Anticancer Drugs"). Other treatments exploit some of the chemicals the body naturally produces. For example, some breast cancer cells thrive on the hormone estrogen, which is produced in the ovaries. Endocrine therapy slows the growth of such cells by preventing them from using estrogen. One of the drugs employed in endocrine therapy is tamoxifen.

Preliminary research has shown that in addition to preventing breast cancer from recurring, tamoxifen may also prevent new cancers from forming in the opposite breast. Chemotherapy involving anti estrogens, such as tamoxifen, has proved useful in delaying breast cancer recurrence, but the majority of patients treated with tamoxifen eventually relapse. Tamoxifen, or Nolvadex, is a drug in pill form, taken orally, that interferes with the activity of estrogen. Tamoxifen has been used to treat both advanced and early stage breast cancer. More recently, it also is being used as adjuvant, or additional, therapy following primary treatment for early stage breast cancer.

Some breast cancer cells are "estrogen sensitive." In other words, estrogen binds to these cells and stimulates them to grow and divide. Tamoxifen prevents the binding of estrogen. This stops the cells from growing and in doing so, prevents or delays breast cancer recurrence. Tamoxifen is also known to work through growth factors and the immune system and may provide some benefit even in patients whose tumors are not estrogen sensitive.

A recent study found that taking tamoxifen for five years significantly reduces both breast cancer recurrence (42%) and mortality (22%) for all women. Results found that in women whose breast cancer has spread to the local lymph glands benefit substantially from tamoxifen therapy. Women who take tamoxifen may share some of the beneficial effects of taking estrogen replacement therapy, such as a decreased risk of osteoporosis and a decreased risk of heart disease. The most common side effect is hot flashes similar to those experienced during menopause. Tamoxifen may induce menopause in a woman who is close to menopause. Other common side effects include vaginal dryness, irregular periods, and weight gain.

In addition, women taking tamoxifen may be at slightly increased risk of developing cataracts. Many experts believe tamoxifen may increase the risk of uterine cancer. There have been some reports of uterine cancer in women taking tamoxifen, however, the incidence is less than 1% in women. A similar drug called Raloxifene, also an anti estrogenic drug, is also being tested for effectiveness. Raloxifene decreased the risk of estrogen receptor-positive breast cancer by 90% (Cummings). New approaches involving reprogramming of the tumor cell genes and targeting of the blood vessels that feed tumors provide hope for more effective and less toxic therapy.

One of the newest forms of breast cancer treatments is a monoclonal antibody called trastuzumab and marketed under the brand name Herceptin. This drug targets cells that overproduce HER-2, a protein implicated in about one-third of all breast cancer cases. Although still under study, Herceptin, helps make chemotherapy more effective by shrinking tumors and slowing the progression of the disease. An advisory committee of the FDA has recommended that Herceptin be approved for use; it will be most effective in a type of breast cancer that afflicts about 30 percent of breast cancer patients. Herceptin reverses the process, by starting with a discovery about the basic genetics of cancer, and then designing a drug to counteract the abnormality. The key in this case is a gene called HER-2/neu.

The gene carries instructions for a protein that sits on the surface of a cell and receives signals from "growth factor" molecules. Thus the HER-2/neu gene and protein play a key role in the fundamental threat of cancer: tumor cells that grow out of control. Meanwhile, researchers are continuing to study the drug to see if it can improve the prognosis of women with earlier stage breast cancers. Experts point out that although Herceptin is unlikely to cure women with metastatic breast cancer, the results of the trials so far are a clear sign of progress. Normal cells carry two copies of HER-2/neu, and have a small number of the HER-2/neu protein receptors on their surfaces.

But researchers found that some cancers have extra copies of the gene and an overabundance of cell surface receptors. The abnormality is not inherited; rather, it is an error acquired during the lives of some people. Researchers estimate that 20 to 30 percent of women with breast cancer have extra HER-2/neu genes in their tumors, amounting to as many as 60-thousand cases a year in the United States. UCLA researchers say women with cancers that "over express" HER-2/neu are more likely to suffer relapses after treatment and do not survive as long as women with normal amounts of the gene. Researchers then set out to find a way to block the HER-2/neu receptors, and thus dampen the signals telling the tumor cells to keep growing. They developed a molecule called a monoclonal antibody that is in essence a mirror image of the HER-2/neu receptor.

Researchers think that when the antibody, Herceptin, attaches to the receptor, like a key fitting a lock, it prevents growth factor molecules from attaching. If Herceptin is approved by the Food and Drug Administration, it will be the first treatment that specifically targets this aggressive form of breast cancer that is associated with more rapid cancer progression and shortened survival. It is the first therapy that was developed to target a specific protein defect that contributes to the malignant progression of cancer. Herceptin was generally well tolerated among patients in both trials.

Overall, the most common adverse reactions related to Herceptin were chills and fever in 40 percent of patients, primarily with the first infusion. Side effects that occur often in women receiving chemotherapy, including hair loss, mouth sores, and low blood cell count levels, were not seen commonly among women taking Herceptin alone. An increased risk of heart dysfunction occurred in women receiving Herceptin (Holtz). In conclusion, there are many new treatments that have been proven to help reduce the harmful effects of breast cancer.

Some of these include taxol, tamoxifen, and Herceptin. When taken with chemotherapy, these new treatments have been proven to reduce the risk of death from breast cancer. Early detection is the key to surviving breast cancer. You should have a doctor or nurse check your breasts at least once a year, starting at the age of twenty, and regular mammograms should be given at the age of fourth. Because of the new treatments discussed, today women diagnosed with early-stage breast cancer are living longer and most can be treated without losing their breast Hopefully, through breast cancer awareness programs breast cancer can be detected early with many new treatments in the near future.

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